Mesenchymal Stem Cells: A Double‐Edged Approach for Managing Cutaneous Leishmaniasis Lesions

Foroutan, Masoud; Majidiani, Hamidreza; Elsheikha, Hany M.; Saeedi-Boroujeni, Ali; Bahadory, Saeed; Saberi, Reza; Shirzadshahrivar, Ana; Mahmoud Hashemi, Seyed; Soudi, Sara

Abstract

Leishmania spp. are intracellular protozoan parasites responsible for leishmaniasis, a globally prevalent vector-borne disease transmitted by phlebotomine sandflies. Within vertebrate hosts, the parasites preferentially infect macrophages and dendritic cells, leading to cell lysis and the formation of disfiguring lesions. Current treatment regimens are hampered by high toxicity, prolonged administration protocols, and severe side effects, underscoring the need for safer and more effective therapeutic alternatives. Mesenchymal stem cells (MSCs), multipotent non-haematopoietic progenitors with fibroblast-like characteristics, possess self-renewal capacity and the ability to differentiate into various functional cell types. Their intrinsic immunomodulatory and antimicrobial properties have positioned MSCs as promising candidates for combating infectious diseases, including leishmaniasis. This review systematically synthesises experimental evidence on the effects of MSCs on Leishmania parasites and the associated lesions, investigates the potential healing mechanisms of MSCs in the context of Leishmania infection, and outlines future research directions in this evolving field. A comprehensive literature search-spanning Scopus, PubMed, Web of Science, and Google Scholar up to 31 May 2024-identified 11 relevant studies: eight from Iran, two from Brazil, and one from Turkey. While Brazilian investigations utilised L. amazonensis, the others focused primarily on L. major, a leading cause of cutaneous leishmaniasis (CL). Across these studies, MSC-based therapy has shown immunomodulatory and antiparasitic effects, influenced by factors such as cell dosage, timing, route of administration, and the parasite burden. Despite promising findings, variability in experimental designs and outcomes highlights the early and exploratory stage of MSC application in CL therapy. Rigorous and standardised research is urgently needed to validate the therapeutic potential of MSCs and to support their clinical translation for leishmaniasis treatment. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Citation

Foroutan, M., Majidiani, H., Elsheikha, H. M., Saeedi-Boroujeni, A., Bahadory, S., Saberi, R., Shirzadshahrivar, A., Mahmoud Hashemi, S., & Soudi, S. (2025). Mesenchymal Stem Cells: A Double‐Edged Approach for Managing Cutaneous Leishmaniasis Lesions. International Wound Journal, 22(6), Article e70709. https://doi.org/10.1111/iwj.70709

• Journal Article Type: Article
• Acceptance Date: May 29, 2025
• Online Publication Date: Jun 11, 2025
• Publication Date: 2025-06
• Deposit Date: Jun 13, 2025
• Publicly Available Date: Jun 16, 2025
• Journal: International Wound Journal
• Print ISSN: 1742-4801
• Electronic ISSN: 1742-481X
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 6
• Article Number: e70709
• DOI: https://doi.org/10.1111/iwj.70709
• Keywords: cutaneous leishmaniasis | immunomodulation | leishmania | mesenchymal stem cells | stem cell therapy Abbreviations: AD-MSCs, adipose-derived mesenchymal stromal cells; AMPs, antimicrobial peptides; BM-MSCs, bone marrow-derived mesenchymal stromal cells; CD, cluster differentiation; CL, cutaneous leishmaniasis; DCs, dendritic cells; IFN-γ, interferon-gamma; IL, interleukin; il, intralesional; iv, intravenous; L major, Leishmania major; MCL, mucocutaneous leishmaniasis; MQs, macrophages; MSCs, mesenchymal stem cells; NO, nitric oxide; Th, T-helper cell; TLRs, Toll-like receptors; TNF-α, tumour necrosis factor-alpha; VL, visceral leishmaniasis
• Public URL: https://nottingham-repository.worktribe.com/output/50175981
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/iwj.70709